TY - JOUR
T1 - Intravenous minocycline in acute stroke
T2 - a randomized, controlled pilot study and meta-analysis
AU - Kohler, Edith
AU - Prentice, David A
AU - Bates, Timothy R
AU - Hankey, Graeme J
AU - Claxton, Anne
AU - van Heerden, Jolandi
AU - Blacker, David
PY - 2013/9
Y1 - 2013/9
N2 - BACKGROUND AND PURPOSE: Minocycline, in animal models and 2 small randomized controlled human trials, is a promising neuroprotective agent in acute stroke. We analyzed the efficacy and safety of intravenous minocycline in acute ischemic and hemorrhagic stroke.METHODS: A multicenter prospective randomized open-label blinded end point evaluation pilot study of minocycline 100 mg administered intravenously, commenced within 24 hours of onset of stroke, and continued 12 hourly for a total of 5 doses, versus no minocycline. All participants received routine stroke care. Primary end point was survival free of handicap (modified Rankin Scale, ≤2) at day 90.RESULTS: Ninety-five participants were randomized; 47 to minocycline and 48 to no minocycline. In the intention-to-treat population, 29 of 47 (65.9%) allocated minocycline survived free of handicap compared with 33 of 48 (70.2%) allocated no minocycline (rate ratio, 0.94; 95% confidence interval, 0.71-1.25 and odds ratio, 0.73; 95% CI, 0.31-1.71). A meta-analysis of the 3 human trials suggests minocycline may increase the odds of handicap-free survival by 3-fold (odds ratio, 2.99; 95% CI, 1.74-5.16) but there was substantial heterogeneity among the trials.CONCLUSIONS: In this pilot study of a small sample of acute stroke patients, intravenous minocycline was safe but not efficacious. The study was not powered to identify reliably or exclude a modest but clinically important treatment effect of minocycline. Larger trials would improve the precision of the estimates of any treatment effect of minocycline.CLINICAL TRIAL REGISTRATION URL: http://www.anzctr.org.au. Unique identifier: ACTRN12612000237886.
AB - BACKGROUND AND PURPOSE: Minocycline, in animal models and 2 small randomized controlled human trials, is a promising neuroprotective agent in acute stroke. We analyzed the efficacy and safety of intravenous minocycline in acute ischemic and hemorrhagic stroke.METHODS: A multicenter prospective randomized open-label blinded end point evaluation pilot study of minocycline 100 mg administered intravenously, commenced within 24 hours of onset of stroke, and continued 12 hourly for a total of 5 doses, versus no minocycline. All participants received routine stroke care. Primary end point was survival free of handicap (modified Rankin Scale, ≤2) at day 90.RESULTS: Ninety-five participants were randomized; 47 to minocycline and 48 to no minocycline. In the intention-to-treat population, 29 of 47 (65.9%) allocated minocycline survived free of handicap compared with 33 of 48 (70.2%) allocated no minocycline (rate ratio, 0.94; 95% confidence interval, 0.71-1.25 and odds ratio, 0.73; 95% CI, 0.31-1.71). A meta-analysis of the 3 human trials suggests minocycline may increase the odds of handicap-free survival by 3-fold (odds ratio, 2.99; 95% CI, 1.74-5.16) but there was substantial heterogeneity among the trials.CONCLUSIONS: In this pilot study of a small sample of acute stroke patients, intravenous minocycline was safe but not efficacious. The study was not powered to identify reliably or exclude a modest but clinically important treatment effect of minocycline. Larger trials would improve the precision of the estimates of any treatment effect of minocycline.CLINICAL TRIAL REGISTRATION URL: http://www.anzctr.org.au. Unique identifier: ACTRN12612000237886.
KW - Administration, Intravenous
KW - Aged
KW - Aged, 80 and over
KW - Anti-Bacterial Agents/administration & dosage
KW - Brain Ischemia/drug therapy
KW - Cerebral Hemorrhage/drug therapy
KW - Female
KW - Humans
KW - Male
KW - Middle Aged
KW - Minocycline/administration & dosage
KW - Pilot Projects
KW - Severity of Illness Index
KW - Stroke/drug therapy
KW - Treatment Outcome
U2 - 10.1161/STROKEAHA.113.000780
DO - 10.1161/STROKEAHA.113.000780
M3 - Article
C2 - 23868273
SN - 0039-2499
VL - 44
SP - 2493
EP - 2499
JO - Stroke
JF - Stroke
IS - 9
ER -